Using an in vivo canine chambered stomach preparation, the clearance of [14C]aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of [14C]aminopyrine, when topically mixed with acid (pH = 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of "trapping" of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast, when [14C]aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased "trapping" of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.